By Eric Meldrum, Chief Scientific Officer and Stephanie van Dalen, Scientist
Hidradenitis suppurativa overview
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterised by recurrent, painful skin lesions which may lead to irreversible tissue destruction and extensive scarring. One hallmark of HS lesions is the infiltration and activation of neutrophils, which release proinflammatory and cytotoxic neutrophil extracellular traps (NETs) which are macromolecules consisting of the cell’s DNA, citrullinated histones and the granule contents which normally function to kill and digest microbes.
Study overview
In a recent publication in the International Journal of Dermatology, Citryll shared its findings from an investigation of the distribution of NETs in HS patients’ skin, and of the presence of NET markers in blood.
Three biopsies were taken from each HS patient: one within a lesion, one 2cm away from a lesion (perilesional) and one from unaffected skin. In addition, a range of NET markers were tested in patients’ blood.
When stained for evidence of NETs, all layers of lesional and perilesional HS skin were found to be NET positive. This is the first time NETs have been shown to be widely dispersed around HS lesional areas and suggests they may contribute to the propagation of inflammation and lesions.
Blood tests demonstrated that three different markers were more elevated in HS patients, with increasing disease activity. This indicates that circulating NET markers may be a suitable tool for assessing disease activity and response to therapy.
Next steps
While research is ongoing, this latest data establishes NETs as a promising target for novel anti-inflammatory approaches to treat HS. Citryll has developed CIT-013, a first-in-class therapeutic antibody which targets the citrullinated histones within NETs to inhibit their release and enhance their clearance from inflamed tissue. Phase 1 clinical studies have shown promising results, and a Phase 2a clinical trial is expected to begin before the end of 2025.
The full article can be accessed here: Neutrophil Extracellular Traps are Widely Distributed Across Lesional and Perilesional Hidradenitis Suppurativa Skin and Elevated Serum NET Markers Associate with Moderate to Severe HS Disease